The evaluation of the antimalarial activity of the phenanthrene methanol, halofantrine or 1-[1,3-dichlorotrifluoromethyl-9-phenanthryl]-3-di-(n-butyl)-aminopropanol hydrochloride, was reported in the American Journal of Tropical Medicine and Hygiene, Vol. 31(6) pages 1075-79 (1982). Halofantrine was effective when administered over a short period of time and with a minimum of two doses against the multi-drug resistant Vietnam Smith strain and Cambodian Buchanan strain of P. falciparum and the Chesson strain of P. vivax. However, problems with systemic bioavailability remained. A means for enhancing the bioavailability of a number of phenanthrene methanol antimalarial compounds, including halofantrine, utilizing specific organic fatty acids, as adjuvants, has been disclosed in U.S. Pat. No. 4,178,376.
Mefloquine, .alpha.-2-piperidinyl-2,8-bis(trifluorormethyl)-4-quinoline methanol, has been shown to exhibit antimalarial activity in humans against both chloroquine-sensitive and resistant strains of Plasmodium falciparum.
U.S. Pat. No. 4,507,288 Rossignol discloses .beta.-glycerophosphate salts of the class of antimalarial compounds containing halofantrine (as the free base) and its analogues. Pharmaceutical compositions and treatment of subjects with malaria are also disclosed. Exemplary compounds include 1-[1,3-dichloro-6-trifluoromethyl-9-phenanthryl]-3-di(n-butyl)aminopropano l-.beta.-glycerophosphate and 1-[1,3-dichloro-6-trifluoromethyl-9-phenanthryl]-3-n-butylaminopropanol-.b eta.-glycerophosphate.
U.S. Pat. No. 4,521,424 Rossignol discloses that the quinate salt of .alpha.-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinoline methanol is useful as an antimalarial agent. Pharmaceutical compositions and methods of treatment of subjects with malaria are also disclosed.